DESCRIPTION: The ultimate goal of this new line of research is to understand the neurophysiological basis of memory impairments that occur during the course of normal aging in all mammals, including humans. An extensive series of electrophysiological and behavioral studies in this and other laboratories has provided considerable insight into the pattern of neuronal alterations that occur in the hippocampus of old rats in relation to memory impairments. Over the last 15 years, this research group has been among the leaders in the development of methods for simultaneously recording from many single neurons in the hippocampus and neocortex of behaving rats. With this method, a principal neuronal population correlate of memory retrieval failure during aging has been recently discovered. This finding makes specific predictions for how the dynamics of neural coding between the hippocampus and neocortical structures may be altered in aging mammals. At the present time, there have been no electrophysiological studies of cognitive processes in mature and old nonhuman primates. Neurophysiological studies in the awake, behaving aged monkey will be technically demanding, time consuming and will require significant resources. With the collaboration of the staff at the California Regional Research Primate Center at Davis, and other scientists affiliated with the Center, the present project is designed to demonstrate the feasibility and scientific value of neuronal ensemble recording in young and old monkeys. The specific hypothesis to be tested is that changes in single cell responses in inferotemporal cortex (perirhinal) that occur as a result of associative learning, will be altered in aged memory-impaired primates. Specifically, altered synaptic plasticity of the backward projections from hippocampal formation structures to inferior temporal cortical areas should lead to reduced associative modifications in old neural networks. The extension of these ensemble recording methods to the aged nonhuman primate brain has the potential to lead to important direct insights into the mechanisms of cognitive impairment in aged humans and into possible treatment strategies.